The present invention relates to a method of medical treatment of a patient for diseases related to plasma proteins, and referred to as plasmapheresis.
To appreciate the nature of the present invention, a brief discussion of the makeup of blood is useful. Approximately 45% of the volume of blood is in the form of cellular components. These cellular components include red cells, also referred to as erthrocytes, white cells, also referred to as leukocytes, and platelets. Plasma makes up the remaining 55% of the volume of blood. Basically, plasma is the fluid portion of the blood which suspends the cells and comprises a solution of approximately 90% water, 7% protein and 3% of the various other organic and inorganic solutes.
In the past twenty years, a group of diseases have been identified which are mediated by circulated proteins and subgroups of proteins called antibodies. Many of these disease processes, for which the etiology has not been determined, have been classified as antibody-mediated diseases. An incomplete list of diseases which fall into this category would include: (1) systemic lupus erthematosus, (2) Guillain-Barre Syndrome, (3) myasthenia gravis, (4) polymyositis, (5) acute and chronic glomerulonephbritis, (6) Goodpasture's syndrome, (7) polyarteritis modosa, (8) thrombotic thrombocytopenic purpura, (9) Waldenstrom's macroglobulinemia, (10) schleroderma, (11) rheumatoid arthritis, (12) multiple sclerosis, (13) rheumatic fever, and (14) transplant rejection.
Manipulation of the production of proteins and, therefore, antibodies, became possible with the isolation and production of cortisone. This hormone and its synthetic derivatives are presently used to decrease the production and reaction of the harmful antibodies produced in the above-mentioned disease processes. Other non-cortisone drugs (immunosuppressants) first developed as cancer chemotherapy are also used to decrease the production of these antibodies. Both cortisone and immunosuppressive drugs have substantial risks and side-effects, but are presently used as the first line approach in the treatment of diseases related to antibody production.
In the late 1950's and early 1960's, it was discovered that mechanical removal of abnormal antibodies in certain disease processes could be beneficial. This was first used in the treatment of Waldenstrom's macroglobulinemia, a disease in which an abnormal protein of very large size (one million molecular weight) is produced. As the concentration of this abnormal protein increases, the blood becomes extremely viscous, producing a syndrome called hyperviscosity syndrome.
During this same period, many of the aforementioned disease processes were identified as being mediated by circulating proteins. Interest arose in the possible clinical effects of protein removal from whole blood, also known as plasmapheresis. Parallel with the development of the plasmapheresis concept was the development of sophisticated blood banking in which component therapy was defined (i.e., isolation of platelets and white blood cells, red blood cell separation, washing, storing and freezing). These new therapeutic modalities stimulated the development of technology to rapidly separate the plasma component of whole blood from the cellular components.
Separation of blood into a plasma fraction and a cellular component fraction is desirable for many medical reasons. For example, separation of blood into plasma fractions and cellular component fraction provides for a collection of plasma alone, with the cellular components being returned to the donor with a suitable portion of replacement fluid. This process is broadly referred to as "plasmapheresis. " Thus, plasmapheresis provides for the collection of plasma from donors without the removal of the cellular components from the diseased plasma and returning the cellular components to the patient in admixture with a suitable replacement fluid, or by further fractionating the patient's plasma to remove the unwanted substances and returning a major portion of the patient's plasma with the cellular components. Finally, a plasmapheresis process can be employed for diagnostic purposes wherein plasma is separated from the cellular components and analyzed to detect disease-causing substances or conditions therein.
Heretofore, plasmapheresis has been accomplished extracorporeally primarily by removal of a quantity of blood from a patient, separating the cellular component from the plasma component and returning the cellular component to the patient. In some cases, replacement of the removed plasma is required. In a manual method of plasmapheresis, the desired amount of blood is removed by venipuncture. The cellular components are separated from the plasma component by a centrifuge. The plasma portion is manually removed from the centrifuge, and the cellular component is returned to the patient. Fresh plasma or a fluid supplement is returned to the patient along with the cellular component as a replacement for the separated plasma.
Plasmapheresis has also been conducted by a cell separator method. In this process, circulatory access to a patient is achieved. Instrumentation connected to the patient provides either continuous flow centrifugation or intermittent flow centrifugation. In continuous flow centrifugation, a quantity of blood is removed to a centrifugal element. Blood centrifugal and plasma are removed by a peristaltic pump to a collection container. From there, the cellular component of the blood and replacement fluid are returned to the patient. In intermittent flow centrifugation, a quantity of blood is removed to a centrifugal element by a blood pump. Operation of the centrifuge is intermittently discontinued to retrieve the cellular component, which is returned to the patient along with replacement fluids. The separated plasma is drained to a waste collection container.
Another method of plasmapheresis involves the use of an external membrane. Circulatory access to the patient is achieved and attachment is made to instrumentation including a pair of blood pumps and a plasma separator comprising a membrane. The blood removed from the patient is introduced to a membrane cell separator. Cellular components of the blood are rejected from the membrane with plasma being filtered through. The plasma is returned to a waste collection container. The cellular component is returned to the patient along with the replacement fluid.
In summary, plasmapheresis as it has heretofore been practiced involves taking blood from the body, and passing it into a separation device which separates the plasma from cellular aspects. Two things can happen then. One is to throw away the plasma, replace it with a substitute plasma, and reinfuse this into the body. By this procedure, it is possible to replace the plasma of the body, which is useful in a large number of disease states, mainly those which are manifested by the presence of large protein molecules in the body which have very adverse clinical effects. Alternatively, the offending molecules are removed from the plasma. Then, the same plasma is put back into the line and returned to the body. The separation can be made by means of centrifuge or by means of membrane filtration.
The present invention provides an alternative procedure for accomplishing protein removal in the treatment of a patient having a protein mediated disease.